4-Amino-6-methoxypyrimidine → 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(6-methoxypyrimidin-4-yl)isoquinoline-6-sulfonamide

HRID 1473433Notes

Reaction equation

HRID 1473433 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]([NH2:9])[CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:20][O:21][C:22]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:23]=1[C:32]1[C:41]2[C:36](=[CH:37][C:38]([S:42](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:44])=[O:43])=[CH:39][CH:40]=2)[CH:35]=[CH:34][N:33]=1>>[CH3:20][O:21][C:22]1[CH:27]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:25]=[CH:24][C:23]=1[C:32]1[C:41]2[C:36](=[CH:37][C:38]([S:42]([NH:9][C:5]3[CH:4]=[C:3]([O:2][CH3:1])[N:8]=[CH:7][N:6]=3)(=[O:44])=[O:43])=[CH:39][CH:40]=2)[CH:35]=[CH:34][N:33]=1

Participants

4

Reactant 3

HCID 7357314-Amino-6-methoxypyrimidineHCID 2733832Lithium HexamethyldisilazideHCID 86687478Perfluorophenyl 1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline-6-sulfonate

Product 1

HCID 715855331-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(6-methoxypyrimidin-4-yl)isoquinoline-6-sulfonamideYield 6%

Procedure

To a vial containing 6-methoxypyrimidin-4-amine (0.063, 0.503 mmol) in 2Me-THF (1 ml) was added lithium bis(trimethylsilyl)amide (237 μl, 0.237 mmol) at −78° C. and stirred for 1 h. To this was then added a solution of perfluorophenyl 1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline-6-sulfonate (Intermediate LLL; 100 mg, 0.182 mmol) in 2Me-THF (1 ml) at −78° C. dropwise and stirred for 1 h. Reaction mixture was quenched with 3 drops of methanol and purified via reverse-phase chromatography with 0.1% NH4OH in ACN and water as mobile phase to obtain 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(6-methoxypyrimidin-4-yl)isoquinoline-6-sulfonamide (0.005 g, 6%) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.77 (d, J=5.77 Hz, 1H) 8.63 (s, 1H) 8.52-8.56 (m, 1H) 7.82-7.89 (m, 2H) 7.77 (d, J=8.80 Hz, 1H) 7.50 (d, J=7.83 Hz, 1H) 7.41 (d, J=8.12 Hz, 1H) 7.28 (br. s., 2H) 3.96 (s, 3H) 3.75 (s, 3H); m/z (ESI) 491.1 (M+H)+.

Workup

  1. stirringstirred for 1 h
  2. customReaction mixture
  3. customwas quenched with 3 drops of methanol
  4. custompurified via reverse-phase chromatography with 0.1% NH4OH in ACN and water as mobile phase

Sources & evidence

ORD record
ord-f215a68cd39f491c921d4dc9c8e5b371
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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